Neurons communicate through synapses, specialized junctions between presynaptic and postsynaptic neurons. Changes in synapse formation lead to altered synaptic plasticity and circuit formation, which can lead to changes in mood, behavior, and learning & memory. Additionally, some altered states, including disease and drug addiction, arise from alterations in synaptic efficacy. Recent work has identified cell adhesion molecules capable of inducing synapse formation. One of these is SynCAMI, the seminal member of the SynCAM family, which contains four related proteins. The objective of this proposal is to determine whether the individual SynCAMs have different synaptic induction properties and may thus contribute to a molecular code for synapse formation. The proposed studies are thus fundamental to understanding both the normal and diseased brain. Three specific aims will be pursued to achieve this objective. In the first, the ability of the SynCAMs to induce presynaptic and postsynaptic terminals will be uncovered. In the second, the interactions between the SynCAMs that lead to this synapse induction will be determined in vitro. Here, the key question is to what extent each SynCAM preferentially interacts with itself or with others to induce a cellular response. In the third, these relationships between the SynCAMs will be tested in vivo. To address this aim, the localization of these molecules will first be determined. Then, the expression of each will be manipulated to determine whether specific synaptic types can be affected by perturbing SynCAM expression. In conclusion, these studies aim to elucidate fundamental mechanisms mediating induction and differentiation of synapses. [unreadable] [unreadable] [unreadable]